Our objective is to study the DNA damage and repair in various individual genes and in non-coding sequences with the genome. This is correlated to more traditional studies of DNA repair as an average over the genome. It is now established that there is intragenomic heterogeneity of DNA repair. Findings have indicated that active genes are preferentially repaired in mammalian cells and that determinations of DNA repair in specific genes are important for correlations to biological endpoints and to risk assessments. Whereas our earlier studies were limited to UV as a damaging agent, we have now developed methods to study DNA damage and repair after a certain carcinogens and cancer chemotherapeutics that react with the DNA. We are studying the DNA repair of genes in a number of human, cancer prone DNA repair deficient syndromes and in various human and rodent mutant cell lines, some of which are transfected with repair genes. We are also investigating the role of DNA repair in multidrug resistance.